The goal of the proposed projects is to obtain an understanding of the fundamental aspects of carcinogenesis by studying interactions with cells of viruses and virus-related genes important to malignant transformation. Six interrelated but distinct systems will be analyzed to achieve this goal. Dr. J. Coffin will study the inheritance and expression of endogenous retroviruses important in murine leukemia. Dr. R. Schwartz will study the interaction of murine viruses with cell surface proteins and with the immune system. Dr. N. Rosenberg will study molecular events of in vitro transformation of lymphocytes by "nontransforming" virus. Dr. T. Krontiris will study differential expression of virus-like oncogenes in lymphocytes. Dr. E. Androphy will study regulation of expression of genes important in papilloma virus transformation. Finally, Dr. B. Schaffhausen will study function of papovirus T-antigen important for transformation. It is anticipated that joint analysis of these distinct but intellectually interrelated systems will provide novel insights into the natural history of cancer induction.